Several desensitizing techniques have already been proposed.
According to document GB-A-2 099 698 (Melillo), it has been proposed to incorporate an allergen in small particles of some tenth microns of a pharmaceutically acceptable, in particular non-allergenic per se, solid excipient, for instance lactose; then these particles are encapsulated into calibrated capsules, for instance gelatine capsules. These capsules are intended and adapted for an administration only by inhalation, either by an inhaler tube or a nasal spray. This is the nasal way of administration of an allergen.
This way of administration has the following drawbacks:
the quantity of the allergen actually transferred to the target organ, e.g the lungs cannot be precisely controlled PA1 it remains a cumbersome method requiring a fixed inhalation apparatus, and thus cannot be an ambulatory treatment. PA1 it is mandatory to use very high concentrations of the allergen, since a relatively important part of the latter is destroyed in the gastro-enteric path PA1 such concentrations may result in adverse side effects, such as gastro-intestinal upsets PA1 finally, it cannot be determined or controlled what is the amount actually absorbed of the antigen, and thus it is difficult to establish an exact dosage of the latter. PA1 obtaining respectively different solid doses of said allergen, each dose comprising a pharmaceutically acceptable excipient in solid form formulated so as to be disintegrated in less than 5 minutes in the sublingual cavity under the action of saliva, and a controlled fractionated quantity in said allergen, said doses being identical to one another by the excipient, but differing respectively from one another by their fractionated quantities in said allergen PA1 conditioning in a same package respectively different solid doses of said allergen, ranging progressively by their respective contents in said allergen from a lower concentration in said allergen to a higher concentration in the latter PA1 providing several different packages of said solid doses, respectively increasing the dosage in said allergen, the higher concentration of one package of lower dosage being below or equal to the lower concentration of the following package of higher dosage PA1 administering said packages of increasing dosages, at respectively subsequent periods of the treatment, by placing each dose in solid form in the sublingual cavity, and then spitting out, the saliva having dissolved in same cavity the excipient with said allergen. PA1 said allergen is dissolved or suspended into a solvent, so as to obtain a mother solution having a reference concentration in said allergen PA1 successive dilutions of said mother solutions are prepared so as to obtain respectively different diluted solutions having respectively decreasing controlled sub-concentrations in said allergen PA1 for each respective diluted solution, sub-dilutions are prepared so as to obtain respectively different sub-diluted solutions having respectively decreasing controlled fractionated concentrations in said allergen PA1 incorporating said different fractionated sub-dilutions into respectively different lots of said solid excipient, so as to obtain said respectively different solid doses of said allergen. PA1 the therapeutic treatment may be effected with no stress or medical help PA1 once the solid excipient has been disintegrated it leaves a precise quantity of the allergen within the mouth, without any action or manipulation of the patient PA1 once prepared, no solvent or extraneous matter remains on the particles or tablets of allergen PA1 the patient may control and monitor his treatment himself, in cooperation with his physician. PA1 generally speaking, no adverse reaction PA1 accelerated or faster clinical action PA1 one reproducible and effective transfer to the blood, for a predetermined dose of the allergen.
According to document EP-A-0 135 022 (MORAN), it has been proposed to incorporate an allergen into particles of a solid excipient consisting of an acid insoluble polymer. Such a solid dispersion of the allergen is intended only for an oral administration to the target organ or cells, through the gastro-enteric path.
This way of administration of an allergen suffers from the following drawbacks:
Further, stress has been given to the interest that a sublingual application can offer (Glenis, K. et al, Clinical Allergy, 1986, Vol. 16, 483-491) which would make it possible to avoid certain secondary effects of administration of the allergen by injection.
However, the galenic form selected (liquid form) is not entirely satisfactory; when relatively large dosages (i.e., volumes) are reached, a certain part of the liquid is absorbed orally and therefore escapes sublingual application, which make it impossible to control all the treatment factors. Therefore, this is a galenic form assuring very approximate dosages.
However, this method of administration sublingually seems very promising because the salivary IgA should play an important role in the effectiveness of the treatment. The mechanism of desensitizing sublingually, moreover, is approximately the same as that of desensitizing by injection.